Jules Bordet InstituutFree University Brussels (ULB)

Patrick Flamen, MD, PhD

“Integrated Molecular Imaging in Oncology using PET-CT (radiolabeled

peptides) and MRI (DCE-MRI and MRS).”

• Molecular Imaging: What ? Why ? How ? Positron Emission Tomography Functional MRI

• Integration imaging information (PET-MRI) translational and clinical research activities Clinical team (nuc med / functional radiology)

• Radiolabeled biomarkers (peptides) Ga68-labeling

The Ultimate Goal of Molecular Imaging

• Patient tailored medicine

To adapt the treatment to the patient specific characteristics

» From : one treatment for all» To: one patient one treatment

This requires the knowledge of the underlying molecular defects of the cancer

Networking> ULB (équipe cyclotron Erasme)> Européen (Munich / Amsterdam)

+++ Multidisciplinarité +++

X-rays CT MRI PET SPECT

Nuclear Medicine

Echography

Radiology

Spectrum of Medical imaging

STRUCTURAL / MORPHOLOGICAL METABOLIC / MOLECULAR

Imagerie MétaboliqueCaractérisation Métabolique du Nodule

Pulmonaire

adenocarcinoma fibronecrotic nodule

CT

PET

PET-CTthe new standardNuclear Oncology

PET/CT with FDG

CT anatomy

PET metabolism

Fusion

Rectal Cancer Staging

Baseline PET-CT PET-CT after 2 weeks chemo

A B

chimiothérapie

Treatment Response Assessment

Functional MRI : brain tumor

- (B) difusion-weighted imaging- (D&E) MR spectrometry

Structural Imaging

Metabolic Imaging

Functional Imaging

Molecular Imaging

Anatomy; morphology; density

Perfusion; blood flow; contractility

Glucose ; amino acids consumption

Receptor expression; enzymatic activitygene expression; DNA

CT

MR

I

PE

T

Integrated Imaging

PET-CT

Metabolic / Molecular + Structural

MULTIMODALITY IMAGING

PET-MRI

Metabolic / Molecular / Functional

MULTIFUNCTIONAL IMAGING

WHY ? Patient tailored medicine

• To adapt the treatment to the patient specific characteristics

Early treatment response assessment

Predicting treatment response

Ithier Project Study Aim

• Early treatment response assessment

Pre-Treatment 2 Months Post

43 HU 30 HU

Imaging response to Imatinib

Imaging Response to Glivec

Cumulative Proportion Surviving (Kaplan-Meier)

Complete Censored

Group 1, Group 0,0 100 200 300 400 500 600 700

Time

-0,1

0,0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1,0

Cum

ula

tive P

roport

ion S

urv

ivin

g

Time to treatment failure (PD on CT) n=21

P < 0.001PET respondersPET non-responders

Dr. S. Stroobants et al. (Eur J Cancer 2003)PFS according PET response 8 days after start of treatment

Stroobants et al. Eur J Cancer 2003

Functional Imaging to Evaluate Response to Lapatinib

baseline lapatinib at surgery

Cristofanilli M, et al. Breast Cancer Res Treat. 2006;100 Supp 1:S5

Functional MRI for Early Response measurement

M Lemort, Bordet, 2008

V Huyge, 2008 ASCO

Du et al. J Clin Oncol. 2007 Aug 10;25(23):3440-7

Assessment of response adjuvant chemotherapy in Metastatic breast cancer

V Huyge, 2008 ASCO

Bone Metastatic Breast Cancer

PET responders

PET nonresponders

PET response is related to treatment outcome

V Huyge, 2008 ASCO

Ithier Project Study Aim Predicting response to a targeted treatment

By means of the identification the molecular target of the drug

Examples:

her2/neu breast cancer receptor imaging » predicting Herceptine treatment» Radiolabeled trastuzumab (Zirconium-89 ? )

Hormone receptor imaging» predicting response to anti-hormonal treatment

FDG-PET/CT pré-traitement;

Récidive de lymphome.

FDG-PET/CT 6 mois après traitement par radioimmunothérapie avec anticorps marqués à l’Y90; rémission complète.

immuno-PET/CT; dosimétrie avec anticorps marqués au Zr89 pré-traitment.

K Muylle, 2008, Lugano

FDG-PET immuno-PET FDG response-PET

Ga68–labeled markers PET-CT for Molecular Imaging

example: Ga68-DOTA-octreotide

> neuro-endocrine tumors (staging)> breast cancer (related to ER expression)

> prostate cancer

Ithier 2008

GENERATOR PRODUCED PET TRACERS

Ge68-Ga68 generator

BiosynthesisGa68-DOTA-Toc (octreotide)Labeling SSR subtypes 2-5

Retroperitoneal metastatic LN

11 mm largest diameter

Retroperitoneal metastatic LN

Biosynthesis Module coupled to the Ga68-generator

Automated productionLaptop directedQuality Controll GMP

Ithier Project 2008 : Ga68-radiolabeled proteins for molecular cancer imaging

Thanks